Abstract
Ischemia-reperfusion injury is a clinical condition that poses life-threatening risks and can be caused by diseases or operations such as trauma, shock, and gastric dilatation volvulus. The objective of this study was to examine the effect of oxytocin on intestinal damage in rats induced by experimental ischemia-reperfusion injury. Three groups of Wistar albino rats were established: a control group (CTR, n=6), an intestinal ischemia-reperfusion group (I-IR, n=6), and an intestinal ischemia-reperfusion with oxytocin group (I-IR+Oxt, n=6). The I-IR+Oxt group received an intraperitoneal injection of 1 mg/kg oxytocin 30 minutes before anesthesia. In the I-IR and I-IR+Oxt groups, the superior mesenteric artery was ligated for 1 hour to induce ischemia-reperfusion injury, followed by one hour of reperfusion by opening the ligatures. At the end of the reperfusion period, the rats were euthanized, and blood and intestinal tissue samples were collected. From the blood samples, ALT, ALP, AST, LDH, BUN, creatinine, IL-1β, and TNF-α concentrations were evaluated. Tissue samples were analyzed for IL-1β, TNF-α, and MDA activity. Serum and tissue IL-1β and TNF-α concentrations were higher in both the I-IR and I-IR+Oxt groups compared to the CTR group. However, these levels were found to be lower in the I-IR+Oxt group compared to the I-IR group. The histopathological analysis showed that the I-IR+Oxt group had better epithelial regeneration and less inflammatory cell infiltration compared to the I-I/R group. In conclusion, oxytocin inhibited the release of IL-1β and TNF-α and the harmful effect of I/R on intestinal cells.
Ethical Statement
The local animal ethics committee approved the study protocol (2021-130).
Supporting Institution
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Project Number
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Thanks
The authors would like to thank Assoc. Prof. Dr. Wayne Fuller for the English language proofreading.
References
- Alexandropoulos D, Bazigos GV, Doulamis IP, et al (2017): Protective effects of N-acetylcysteine and atorvastatin against renal and hepatic injury in a rat model of intestinal ischemia-reperfusion. Biomed Pharmacother, 89, 673-680.
- Asad M, Shewade DG, Koumaravelou K, et al (2001): Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs. Life Sci, 70, 17–24.
- Bradford MM (1976): A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 72, 248-254.
- Braun JP, Lefebvre HP (2008): Kidney function and damage. 485-529. In: JJ Kaneko, JW Harvey, ML Bruss (Eds.), Clinical Biochemistry of Domestic Animals. Elsevier Academic Press, Burlington.
- Carter CS, Kenkel WM, MacLean EL, et al (2020): Is oxytocin “nature’s medicine”? Pharmacol Rev, 72, 829-861.
- Cassutto BH, Gfeller RW (2003): Use of intravenous lidocaine to prevent reperfusion injury and subsequent multiple organ dysfunction syndrome. J Vet Emerg Crit Care, 13, 137-148.
- Çetinel Ş, Hancıoğlu S, Şener E, et al (2010): Oxytocin treatment alleviates stress-aggravated colitis by a receptor-dependent mechanism. Regul Pept, 160, 146-152.
- Deng F, Lin ZB, Sun QS, et al (2022): The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia-reperfusion injury. Int J Biol Sci, 18, 3981-3992.
- Düşünceli F, İşeri SÖ, Ercan F, et al (2008): Oxytocin alleviates hepatic ischemia–reperfusion injury in rats. Peptides, 29, 1216-1222.
- ELKady AH, Elkafoury BM, Saad DA, et al (2021): Hepatic ischemia-reperfusion injury: effect of moderate-intensity exercise and oxytocin compared to l-arginine in a rat model. Egypt Liver J, 11, 1-15.
- Gardner AK, Schroeder EL (2022): Pathophysiology of intraabdominal hypertension and abdominal compartment syndrome and relevance to veterinary critical care. J Vet Emerg Crit Care, 32, 48-56.
- Gharishvandi F, Abdollahi A, Shafaroodi H, et al (2020): Involvement of 5-HT1B/1D receptors in the inflammatory response and oxidative stress in intestinal ischemia/reperfusion in rats. Eur J Pharmacol, 882, 173265.
- Gonzalez LM, Moeser AJ, Blikslager AT (2015): Animal models of ischemia-reperfusion-induced intestinal injury: Progress and promise for translational research. Am J Physiol Gastrointest Liver Physiol, 308, G63–G75.
- Gregová K, Číkoš Š, Bilecová-Rabajdová M, et al (2015): Intestinal ischemia-reperfusion injury mediates expression of inflammatory cytokines in rats. Gen Physiol Biophys, 34, 95-99.
- Hamilton TR, Thacher CW, Forsee KM, et al (2010): Trauma‐associated acute mesenteric ischemia in a dog. J Vet Emerg Crit Care, 20, 595-600.
- Lapsekili E, Menteş Ö, Balkan M, et al (2016): Role of alkaline phosphatase intestine-isomerase in acute mesenteric ischemia diagnosis. TJTES, 22, 115-120.
- McMichael M, Moore RM (2004): Ischemia–reperfusion injury pathophysiology, part I. J Vet Emerg Crit Care, 14, 231-241.
- Nadatani Y, Watanabe T, Shimada S, et al (2018): Microbiome and intestinal ischemia/reperfusion injury. J Clin Biochem Nutr, 63, 26-32.
- Ohkawa H, Ohishi N, Yagi K (1979): Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351–358.
- Oliveira-Pelegrin GR, Saia RS, Cárnio EC, et al (2013): Oxytocin affects nitric oxide and cytokine production by sepsis-sensitized macrophages. Neuroimmunomodulation, 20, 65-71.
- Pergel A, Kanter M, Yucel AF, et al (2012): Anti-inflammatory and antioxidant effects of infliximab in a rat model of intestinal ischemia/reperfusion injury. Toxicol Ind Health, 28, 923-932.
- Powell A, Armstrong P (2014): Plasma biomarkers for early diagnosis of acute intestinal ischemia. Semin Vasc Surg, 27, 170-175.
- Ragy MM, Aziz NM (2017): Prevention of renal ischemia/perfusion-induced renal and hepatic injury in adult male Albino rats by oxytocin: Role of nitric oxide. J Basic Clin Physiol Pharmacol, 28, 615-621.
- Sayıner S, Gülmez N, Sabit ZA, et al (2019): Effects of Deep-Frying Sunflower Oil on Sperm Parameters In A Mouse Model: Do Probiotics Have A Protective Effect? Kafkas Univ Vet Fak Derg, 25, 857-863.
- Şehirli AÖ, Sayiner S, Savtekin G, et al (2021): Protective effect of bromelain on corrosive burn in rats. Burns, 47, 1352-1358.
- Senturk GE, Erkanli K, Aydin U, et al (2013): The protective effect of oxytocin on ischemia/reperfusion injury in rat urinary bladder. Peptides, 40, 82-88.
- Soares RO, Losada DM, Jordan MC, et al (2019): Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies. Int J Mol Sci, 20, 5034.
- Sookoian S, Pirola CJ (2015): Liver enzymes, metabolomics, and genome-wide association studies: from systems biology to the personalized medicine. World J Gastroenterol, 21, 711-725.
- Tuğtepe H, Şener G, Bıyıklı NK, et al (2007): The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regul Pept, 140, 101-108.
- VanderBroek AR, Engiles JB, Kästner SB, et al (2021): Protective effects of dexmedetomidine on small intestinal ischemia-reperfusion injury in horses. Equine Vet J, 53, 569-578.
Abstract
İskemi-reperfüzyon yaralanması, travma, şok, gastrik dilatasyon volvulus gibi bazı hastalıklar veya operasyonlar nedeniyle yaşamı tehdit eden bir klinik durumdur. Çalışmanın amacı, oksitosinin sıçanlarda deneysel olarak oluşturulan iskemi-reperfüzyon hasarının neden olduğu bağırsak hasarı üzerindeki etkisini araştırmaktı. Üç grup Wistar albino sıçan oluşturuldu: Kontrol (CTR, n=6), bağırsak iskemi-reperfüzyon (I-IR, n=6) ve bağırsak iskemi-reperfüzyon+ Oksitosin (I-IR+Oxt, n=6). I-IR+Oxt grubuna anesteziden 30 dakika önce intraperitoneal olarak oksitosin (1 mg/kg) verildi. I-IR ve I-IR+Oxt gruplarında 1 saat superior mezenterik arter ligasyonu ve ligatürler açılarak 1 saat reperfüzyon ile iskemi reperfüzyonu uygulandı. Reperfüzyon süresinin bitiminden sonra ötenazi yapılarak kan ve barsak doku örnekleri alındı. Kan örneklerinden ALT, ALP, AST, LDH, BUN, kreatinin, IL-1β, TNF-α, konsantrasyonları ve doku örneğinden IL-1β, TNF-α ve MDA aktiviteleri değerlendirildi. Serum ve doku IL-1β, TNF-α konsantrasyonları hem I-IR hem de I-IR+Oxt gruplarında CTR grubuna göre yüksek bulunurken, bu seviyelerin I-IR+Oxt grubunda I-IR+Oxt grubuna göre daha düşük olduğu belirlendi. I-IR grubu. Histopatolojik analiz, I-I/R grubuna kıyasla I-IR+Oxt grubunda hem epitel hem de bez yapısının epitelyal rejenerasyonunun ve inflamatuar hücre infiltrasyonunun azaldığını gösterdi. Sonuç olarak oksitosin, IL-1β ve TNF-α salınımını ve IR'nin bağırsak hücreleri üzerindeki zararlı etkisini engellemiştir.
Project Number
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References
- Alexandropoulos D, Bazigos GV, Doulamis IP, et al (2017): Protective effects of N-acetylcysteine and atorvastatin against renal and hepatic injury in a rat model of intestinal ischemia-reperfusion. Biomed Pharmacother, 89, 673-680.
- Asad M, Shewade DG, Koumaravelou K, et al (2001): Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs. Life Sci, 70, 17–24.
- Bradford MM (1976): A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 72, 248-254.
- Braun JP, Lefebvre HP (2008): Kidney function and damage. 485-529. In: JJ Kaneko, JW Harvey, ML Bruss (Eds.), Clinical Biochemistry of Domestic Animals. Elsevier Academic Press, Burlington.
- Carter CS, Kenkel WM, MacLean EL, et al (2020): Is oxytocin “nature’s medicine”? Pharmacol Rev, 72, 829-861.
- Cassutto BH, Gfeller RW (2003): Use of intravenous lidocaine to prevent reperfusion injury and subsequent multiple organ dysfunction syndrome. J Vet Emerg Crit Care, 13, 137-148.
- Çetinel Ş, Hancıoğlu S, Şener E, et al (2010): Oxytocin treatment alleviates stress-aggravated colitis by a receptor-dependent mechanism. Regul Pept, 160, 146-152.
- Deng F, Lin ZB, Sun QS, et al (2022): The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia-reperfusion injury. Int J Biol Sci, 18, 3981-3992.
- Düşünceli F, İşeri SÖ, Ercan F, et al (2008): Oxytocin alleviates hepatic ischemia–reperfusion injury in rats. Peptides, 29, 1216-1222.
- ELKady AH, Elkafoury BM, Saad DA, et al (2021): Hepatic ischemia-reperfusion injury: effect of moderate-intensity exercise and oxytocin compared to l-arginine in a rat model. Egypt Liver J, 11, 1-15.
- Gardner AK, Schroeder EL (2022): Pathophysiology of intraabdominal hypertension and abdominal compartment syndrome and relevance to veterinary critical care. J Vet Emerg Crit Care, 32, 48-56.
- Gharishvandi F, Abdollahi A, Shafaroodi H, et al (2020): Involvement of 5-HT1B/1D receptors in the inflammatory response and oxidative stress in intestinal ischemia/reperfusion in rats. Eur J Pharmacol, 882, 173265.
- Gonzalez LM, Moeser AJ, Blikslager AT (2015): Animal models of ischemia-reperfusion-induced intestinal injury: Progress and promise for translational research. Am J Physiol Gastrointest Liver Physiol, 308, G63–G75.
- Gregová K, Číkoš Š, Bilecová-Rabajdová M, et al (2015): Intestinal ischemia-reperfusion injury mediates expression of inflammatory cytokines in rats. Gen Physiol Biophys, 34, 95-99.
- Hamilton TR, Thacher CW, Forsee KM, et al (2010): Trauma‐associated acute mesenteric ischemia in a dog. J Vet Emerg Crit Care, 20, 595-600.
- Lapsekili E, Menteş Ö, Balkan M, et al (2016): Role of alkaline phosphatase intestine-isomerase in acute mesenteric ischemia diagnosis. TJTES, 22, 115-120.
- McMichael M, Moore RM (2004): Ischemia–reperfusion injury pathophysiology, part I. J Vet Emerg Crit Care, 14, 231-241.
- Nadatani Y, Watanabe T, Shimada S, et al (2018): Microbiome and intestinal ischemia/reperfusion injury. J Clin Biochem Nutr, 63, 26-32.
- Ohkawa H, Ohishi N, Yagi K (1979): Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351–358.
- Oliveira-Pelegrin GR, Saia RS, Cárnio EC, et al (2013): Oxytocin affects nitric oxide and cytokine production by sepsis-sensitized macrophages. Neuroimmunomodulation, 20, 65-71.
- Pergel A, Kanter M, Yucel AF, et al (2012): Anti-inflammatory and antioxidant effects of infliximab in a rat model of intestinal ischemia/reperfusion injury. Toxicol Ind Health, 28, 923-932.
- Powell A, Armstrong P (2014): Plasma biomarkers for early diagnosis of acute intestinal ischemia. Semin Vasc Surg, 27, 170-175.
- Ragy MM, Aziz NM (2017): Prevention of renal ischemia/perfusion-induced renal and hepatic injury in adult male Albino rats by oxytocin: Role of nitric oxide. J Basic Clin Physiol Pharmacol, 28, 615-621.
- Sayıner S, Gülmez N, Sabit ZA, et al (2019): Effects of Deep-Frying Sunflower Oil on Sperm Parameters In A Mouse Model: Do Probiotics Have A Protective Effect? Kafkas Univ Vet Fak Derg, 25, 857-863.
- Şehirli AÖ, Sayiner S, Savtekin G, et al (2021): Protective effect of bromelain on corrosive burn in rats. Burns, 47, 1352-1358.
- Senturk GE, Erkanli K, Aydin U, et al (2013): The protective effect of oxytocin on ischemia/reperfusion injury in rat urinary bladder. Peptides, 40, 82-88.
- Soares RO, Losada DM, Jordan MC, et al (2019): Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies. Int J Mol Sci, 20, 5034.
- Sookoian S, Pirola CJ (2015): Liver enzymes, metabolomics, and genome-wide association studies: from systems biology to the personalized medicine. World J Gastroenterol, 21, 711-725.
- Tuğtepe H, Şener G, Bıyıklı NK, et al (2007): The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regul Pept, 140, 101-108.
- VanderBroek AR, Engiles JB, Kästner SB, et al (2021): Protective effects of dexmedetomidine on small intestinal ischemia-reperfusion injury in horses. Equine Vet J, 53, 569-578.
Details
| Primary Language | English |
|---|---|
| Subjects | Veterinary Biochemistry, Veterinary Surgery, Veterinary Pharmacology, Veterinary Histology and Embryology |
| Journal Section | Research Article |
| Authors | |
| Project Number | - |
| Early Pub Date | October 27, 2023 |
| Publication Date | July 10, 2024 |
| Published in Issue | Year 2024 |